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III-A. RETROSYNTHETIC ANALYSIS

• Disconnection: An analytical operation, which breaks a bondand converts a molecule into a possible starting material. Thereverse of a chemical reaction. Symbol ⇒ and a curved linedrawn through the bond being broken.

Definitions

• FGI: Functional Group Interconversion: The operation of writing onefunctional group for another so that disconnection becomes possible. Thereverse of a chemical reaction. Symbol ⇒ with FGI written over it.• Reagent: A compound which reacts to give an intermediate in theplanned synthesis or to give the target molecule itself. The syntheticequivalent of a synthon.• Synthetic equivalent: A reagent carrying out the function of a synthonwhich cannot itself be used, often because it is too unstable.•Synthon: A generalized fragment, usually an ion, produced by adisconnection. (some people also use synthon for a synthetic equivalent).•Target Molecule: The molecule whose synthesis is being planned.

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Retrosynthesis is the process of “deconstructing” a targetmolecule into readily available starting materials by means of

- imaginary breaking of bonds (disconnections) and by the conversion ofone functional group into another (functional group interconversions).

The following factors need be taken into consideration:

Efficiency, e.g. the “arithmetic demon”:“The arithmetic demon dictates one of the major axioms of synthesis: Getthe most done in the fewest steps and in the highest yield.” (R. E.Ireland)

Retrosynthesis

A linear synthesis with 14 starting materials and intermediates:

yield = (0.8)14 = 4%

Dr. P. Wipr Chem 2320 4/16/2007

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A convergent synthesis with 14 starting materials andintermediates:

yield = (0.8)3 = 51%

Question: If every reaction goes with a 60% yield, what is themore efficient strategy:

or

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Dr. P. Wipr Chem 2320 4/16/2007

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Carpanone: Chapman, O. et al. J. Am. Chem. Soc. 1971, 93,6696.

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Mechanism:

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